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Stiffness-tunable biomaterials provide a good extracellular matrix environment for axon growth and regeneration

Neural Regeneration Research 2025年第5期20卷 1364-1376页

作者： Ronglin han Lanxin Luo Caiyan Wei Yaru Qiao Jiming Xie Xianchao Pan Juan Xing Department of Pathophysiology School of Basic Medical SciencesSouthwest Medical UniversityLuzhouSichuan ProvinceChina Department of Medicinal Chemistry School of PharmacySouthwest Medical UniversityLuzhouSichuan ProvinceChina

Neuronal growth, extension, branching, and formation of neural networks are markedly influenced by the extracellular matrix—a complex network composed of proteins and carbohydrates secreted by cells. In addition to providing physical support for cells, the extracellular matrix also conveys critical mechanical stiffness cues. During the development of the nervous system, extracellular matrix stiffness plays a central role in guiding neuronal growth, particularly in the context of axonal extension, which is crucial for the formation of neural networks. In neural tissue engineering, manipulation of biomaterial stiffness is a promising strategy to provide a permissive environment for the repair and regeneration of injured nervous tissue. Recent research has fine-tuned synthetic biomaterials to fabricate scaffolds that closely replicate the stiffness profiles observed in the nervous system. In this review, we highlight the molecular mechanisms by which extracellular matrix stiffness regulates axonal growth and regeneration. We highlight the progress made in the development of stiffness-tunable biomaterials to emulate in vivo extracellular matrix environments, with an emphasis on their application in neural repair and regeneration, along with a discussion of the current limitations and future prospects. The exploration and optimization of the stiffness-tunable biomaterials has the potential to markedly advance the development of neural tissue engineering.

关键词： alginate axon growth biomaterials extracellular matrix neural repair neurons neuroregeneration polyacrylamide polydimethylsiloxane stiffness

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Combination of fruquintinib with venetoclax for the treatment of colorectal cancer

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Oncology Research 2025年第1期33卷 225-234页

作者： WEI ZhanG WEICHENG WANG RUI WANG XIAO han LIJUN ZHU wenJIE GUO YANHONG GU Department of Oncology The First Affiliated Hospital of Nanjing Medical UniversityNanjing210029China State Key Laboratory of Pharmaceutical Biotechnology School of Life SciencesNanjing UniversityNanjing210023China Department of Oncology The Affiliated Taizhou People’s Hospital of Nanjing Medical UniversityTaizhou225300China

Background:As a novel blocker of vascular endothelial growth factor receptor(VEGFR),fruquintinib has been approved for treating colorectal cancer(CRC).However,its dosage and therapeutic efficacy are limited by its widespread adverse ***,recognized as the initial inhibitor of B-cell lymphoma protein 2(BCL2),has shown potential in boosting the effectiveness of immunotherapy against *** study investigated the efficacy and mechanisms of fruquintinib combined with venetoclax in treating *** and Materials:We developed a colon cancer mouse model with the CT26 colon cell line to demonstrate fruquintinib and venetoclax’s efficacy against *** we employed various techniques to evaluate different aspects of the experimental *** was used to detect cell proliferation and angiogenesis in tumor *** blot analysis was utilized to examine the occurrence of cell apoptosis,and flow cytometry to quantitate immune cells within the tumor ***,immunofluorescence was employed to measure cytokine ***:The strongest inhibition on tumor growth was achieved by the combination of fruquintinib with venetoclax,as opposed to individual drug *** was found to amplify the impact of fruquintinib,leading to decreased cancer cell proliferation,increased cancer cell apoptosis,lowered angiogenesis,better vascular structure normalization,and improved immune cell ***:Our findings indicate that the addition of venetoclax enhances the impact of fruquintinib on vascular normalization and modulation of the tumor immune *** study presents the justification for utilizing the fruquintinib and venetoclax combination in treating *** holds promise in being assimilated into anticancer medications for CRC.

关键词： Colorectal cancer(CRC) B-cell lymphoma protein 2(BCL2) Venetoclax Vascular endothelial growth factor receptor(VEGFR) Fruquintinib Anti-angiogenesis Immunotherapy

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Trinuclear gold-catalyzed site-selective alkylation of peptides

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Science China Chemistry 2025年第1期68卷 249-256页

作者： Qing-Yun Fang Chengyihan Gu Yinghan Chen wencheng Yan Yong Liang Weipeng Li Chengjian Zhu Jie han Jin Xie State Key Laboratory of Coordination Chemistry Jiangsu Key Laboratory of Advanced Organic Materials Chemistry and Biomedicine Innovation Center (Chem BIC) School of Chemistry and Chemical Engineering Nanjing University Green Catalysis Center College of Chemistry Zhengzhou University State Key Laboratory of Natural Medicines China Pharmaceutical University

Selective modification of peptides has always been a challenging issue. The selective alkylation of peptides can alter the biological activity and physical properties of molecules, and it has gained significant research interest. We herein disclose an intriguing gold-catalyzed alkylation of peptides using bench-stable unactivated alkyl bromides under photoredox catalysis. A wide range of structurally diverse primary, secondary and tertiary alkyl bromides serve as effective coupling partners to precisely connect with the α-C(sp3)–H in glycine residue of peptides. This protocol demonstrates an exceptionally broad scope for alkyl halides and excellent tolerance for a wide range of useful functional groups. A series of relay transformations to construct cyclic peptides, to proceed click reaction and to realize peptide fluorescence labeling further enhance its synthetic practicality. In addition, mechanistic studies and density functional theory(DFT) calculations reveal an inner-sphere and subsequent outersphere single electron transfer(SET) mechanism.

关键词： gold catalysis peptide alkylation C-C coupling radical

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Bacterial indole-3-propionic acid inhibits macrophage IL-1β production through targeting methionine metabolism

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Science China Life Sciences 2025年

作者： Ziyi han Jian Fu Aiyan Gong wenkai Ren State Key Laboratory of Livestock and Poultry Breeding College of Animal Science South China Agricultural University Animal Disease-resistant Nutrition Key Laboratory of Sichuan Province Sichuan Agricultural University China Institute of Veterinary Drug Control

The gut microbiota plays key roles in host health by shaping the host immune responses through their metabolites, like indole derivatives from tryptophan. However, the direct role of these indole derivatives in macrophage fate decision and the underlying mechanism remains unknown. Here, we found that bacterial indole-3-propionic acid(IPA) downregulates interleukin-1beta(IL-1β) production in M1 macrophages through inhibition of nuclear factor-kappa B(NF-κB) signaling. Mechanistically, IPA binds specifically with methionine adenosyltransferase 2A(MAT2A) to promote S-adenosylmethionine(SAM) synthesis, which facilitates the DNA methylation of ubiquitin-specific peptidase 16(USP16, a deubiquitinase), and in turn promotes Toll-like receptor 4(TLR4) ubiquitination and NF-κB inhibition. Furthermore,IPA administration attenuates sepsis in mouse models induced by lipopolysaccharides(LPS), showcasing its potential as a microbial-derived adjunct in alleviating inflammation. Collectively, our findings reveal a newly found microbial metabolite-immune system regulatory pathway mediated by IPA.

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Novel flexible and transparent microstrip low-pass filter design with Π-shaped DGS

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The Journal of China Universities of Posts and Telecommunications 2025年

作者： Liu Zhaohan han Yunan Qiu Xianbo Li Xianli College of Information Science and Technology， Beijing University of Chemical Technology

This paper proposes a new design for a transparent low-pass filter (LPF) using a flexible PTFE material and metallic copper. The transparent microstrip filter employs an asymmetric Π-shaped structure with dimensions of 260 mm × 13 mm × 0.148 mm， which owns a narrow transition band and achieves an insertion loss of less than 1.0 dB below 0.26 GHz. Furthermore， the insertion loss of the transparent microstrip filter can exceed 30 dB in the stopband of 1.02 GHz to 6.50 GHz. Square holes are added to the copper layer to improve the transparency of the LPF， and the filter performance can be adjusted by changing the square hole area and resolution. Additionally， multiple identical structures are cascaded to increase the insertion loss in the stopband while maintaining the passband. The transparent microstrip LPF has the characteristics of flexibility， high transparency， and significant insertion loss in the stopband， making it suitable for applications that require electromagnetic protection in a clear field of vision.

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High-precision tip positioning composite feedforward control of linear colocated motion systems with Bi-Loop iterative feedforward tuning

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Science China Technological Sciences 2025年

作者： Junyu HU Yourui TAO Shanhu LI Xu han College of Mechanical and Vehicle Engineering Hunan University State Key Laboratory of Reliability and Intelligence of Electrical Equipment Hebei University of Technology

To enhance the tip positioning accuracy and robustness against disturbances of linear colocated motion systems, a novel composite feedforward (COMFF) control with Bi-Loop iterative feedforward tuning (IFFT) is proposed. The tip positioning error consists of the coupled tip residual vibration and linear motor tracking error. Given the influence of nonlinear friction and load flexibility, the topology of COMFF is designed as decoupled structures so that COMFF can suppress the tip residual vibration and compensate for the linear motor tracking error compatibly. Furthermore, Bi-Loop IFFT is built to improve the robustness of COMFF in high-precision motor tracking performance. In the state space of the linear motor tracking error based on the projection theorem, two loops are performed in parallel along the iteration direction. One is the P-type iteration loop that drives linear motor tracking errors to converge to the zero state. The other is the observation loop constructed by the recursive least square with forgetting factors to accelerate the P-type iteration loop. Driven by the P-type iteration loop with the aid of the observation loop, the proposed COMFF is integrated with fast convergence and high robustness when confronted with model disturbances. The effectiveness of the proposed COMFF combined with Bi-Loop IFFT is validated by experiments.

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Peripheral mitochondrial DNA as a neuroinflammatory biomarker for major depressive disorder

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Neural Regeneration Research 2025年第6期20卷 1541-1554页

作者： Jinmei Ye Cong Duan Jiaxin han Jinrong Chen Ning Sun Yuan Li Tifei Yuan Daihui Peng Division of Mood Disorder Shanghai Mental Health CenterShanghai Jiao Tong University School of MedicineShanghaiChina Department of Psychiatry First Hospital of Shanxi Medical UniversityTaiyuanShanxi ProvinceChina Shanghai Key Laboratory of Psychotic Disorders Brain Health InstituteNational Center for Mental DisordersShanghai Mental Health CenterShanghai Jiao Tong University School of MedicineShanghaiChina Co-Innovation Center of Neuroregeneration Nantong UniversityNantongJiangsu ProvinceChina

In the pathogenesis of major depressive disorder, chronic stress-related neuroinflammation hinders favorable prognosis and antidepressant response. Mitochondrial DNA may be an inflammatory trigger, after its release from stress-induced dysfunctional central nervous system mitochondria into peripheral circulation. This evidence supports the potential use of peripheral mitochondrial DNA as a neuroinflammatory biomarker for the diagnosis and treatment of major depressive disorder. Herein, we critically review the neuroinflammation theory in major depressive disorder, providing compelling evidence that mitochondrial DNA release acts as a critical biological substrate, and that it constitutes the neuroinflammatory disease pathway. After its release, mitochondrial DNA can be carried in the exosomes and transported to extracellular spaces in the central nervous system and peripheral circulation. Detectable exosomes render encaged mitochondrial DNA relatively stable. This mitochondrial DNA in peripheral circulation can thus be directly detected in clinical practice. These characteristics illustrate the potential for mitochondrial DNA to serve as an innovative clinical biomarker and molecular treatment target for major depressive disorder. This review also highlights the future potential value of clinical applications combining mitochondrial DNA with a panel of other biomarkers, to improve diagnostic precision in major depressive disorder.

关键词： biomarker cytokine exosomes inflammasome major depressive disorder microglia mitochondrial DNA mitochondrial dysfunction neuroinflammation Toll-like receptor

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AAV2-PDE6B restores retinal structure and function in the retinal degeneration 10 mouse model of retinitis pigmentosa by promoting phototransduction and inhibiting apoptosis

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Neural Regeneration Research 2025年第8期20卷 2408-2419页

作者： Ruiqi Qiu Mingzhu Yang Xiuxiu Jin Jingyang Liu Weiping Wang Xiaoli Zhang Jinfeng han Bo Lei Henan Eye Hospital Henan Provincial People’s HospitalPeople’s Hospital of Zhengzhou UniversityZhengzhouHenan ProvinceChina Eye Institute Henan Academy of Innovations in Medical ScienceZhengzhouHenan ProvinceChina Branch of National Clinical Research Center for Ocular Disease Henan Provincial People’s HospitalZhengzhouHenan ProvinceChina Academy of Medical Science Zhengzhou UniversityZhengzhouHenan ProvinceChina

Retinitis pigmentosa is a group of inherited diseases that lead to retinal degeneration and photoreceptor cell ***,there is no effective treatment for retinitis pigmentosa caused by PDE6B ***-associated virus(AAV)-mediated gene therapy is a promising strategy for treating retinitis *** aim of this study was to explore the molecular mechanisms by which AAV2-PDE6B rescues retinal *** do this,we injected retinal degeneration 10(rd10)mice subretinally with AAV2-PDE6B and assessed the therapeutic effects on retinal function and structure using dark-and light-adapted electroretinogram,optical coherence tomography,and ***-independent acquisition-mass spectrometry-based proteomic analysis was conducted to investigate protein expression levels and pathway enrichment,and the results from this analysis were verified by real-time polymerase chain reaction and western ***2-PDE6B injection significantly upregulated PDE6βexpression,preserved electroretinogram responses,and preserved outer nuclear layer thickness in rd10 *** expressed proteins between wild-type and rd10 mice were closely related to visual perception,and treating rd10 mice with AAV2-PDE6B restored differentially expressed protein expression to levels similar to those seen in wild-type *** Encyclopedia of Genes and Genome analysis showed that the differentially expressed proteins whose expression was most significantly altered by AAV2-PDE6B injection were enriched in phototransduction ***,the phototransductionrelated proteins Pde6α,Rom1,Rho,Aldh1a1,and Rbp1 exhibited opposite expression patterns in rd10 mice with or without AAV2-PDE6B ***,Bax/Bcl-2,p-ERK/ERK,and p-c-Fos/c-Fos expression levels decreased in rd10 mice following AAV2-PDE6B *** data suggest that AAV2-PDE6B-mediated gene therapy promotes phototransduction and inhibits apoptosis by inhibiting the ERK signaling pathway and upr

关键词： apoptosis AAV2-PDE6B ERK1/2 gene therapy phototransduction proteomics rd10 retinitis pigmentosa

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Synergistic promotion strategy of “dual-site” and “dual-path” to enhance the C–C coupling between CO2 and HCHO driven by photoelectrocatalysis

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Journal of Energy Chemistry 2025年第1期100卷 39-49页

作者： Hongqiang Yang Jianfeng Zheng Guoyu Wang Yifei Gao Yatao Yang Jia Li Xiaojin han Yan Cui Zhanggen Huang National Key Laboratory of High Efficiency and Low Carbon Utilization of Coal Institute of Coal Chemistry Chinese Academy of Science University of Chinese Academy of Science Shenyang University of Chemical Technology

Photoelectrocatalytic coupling CO2and volatile organic compounds （VOCs） is a promising green strategy for the synergistic conversion of the two carbon-containing resources to *** catalytic efficiency is always at the mercy of chemical inertness of CO2and the competitive hydrogen evolution of ***,a modified g-C3N4/ZnAl-LDH Z-scheme heterojunction catalyst with dual reaction site was rationally designed and precisely *** Faraday efficiency of ethanol reached 68.67%with a corresponding formation rate of 227.3μmol *** revealed by in-situ characterizations and density functional theory calculations,CO2and HCHO were absorbed at Zn site and N site,***,*CO generated from CO2and HCHO was converted to*CH3O and*CHO on the dual-active-site *** detailed reaction mechanism experiments indicated that C–C coupling only occurred between*CO and*CH3O in electrocatalysis *** from the“*CO+*CH3O”path,another“*CO+*CHO”coupling path was also detected in photoelectrocatalytic *** selectivity of ethanol was significantly enhanced due to the synthesis of dual-site catalyst and the dual-path coupling path between CO2and HCHO simultaneously driven by light and electricity.

关键词： Ethanol

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基于地理分区的陕北黄土高原生态系统服务权衡/协同的尺度效应研究

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水土保持研究 2025年第1期32卷 305-315页

作者：温昕王继军韩晓佳中国科学院水土保持与生态环境研究中心陕西杨凌712100 中国科学院水利部水土保持研究所陕西杨凌712100 西北农林科技大学水土保持研究所陕西杨凌712100 中国科学院大学北京100049 中国科学院生态环境研究中心北京100085

[目的]明晰生态系统服务的权衡/协同关系,保证生态系统服务长期有效供应,实现流域生态保护与高质量发展。[方法]以典型退耕区陕北黄土高原为例,利用1990-2020年土地利用变化数据,基于InVEST模型量化4种关键生态系统服务即碳储量、产水... 详细信息

[目的]明晰生态系统服务的权衡/协同关系,保证生态系统服务长期有效供应,实现流域生态保护与高质量发展。[方法]以典型退耕区陕北黄土高原为例,利用1990-2020年土地利用变化数据,基于InVEST模型量化4种关键生态系统服务即碳储量、产水量、土壤保持量和生境质量的时空分布特征,通过相关性分析探讨了各类生态系统服务间的权衡/协同关系和呈现的尺度特征。[结果](1)1990-2020年碳储量和生境质量处于不断增加的趋势,产水量和土壤保持量呈现先降低后增加总体增加的趋势,空间上呈东南略低西北略高的分布。(2)陕北黄土高原生态系统服务以协同作用为主,且在1990-2020年协同效应不断增强,权衡作用主要发生在产水量与其他生态系统服务之间,权衡作用的区域主要分布在研究区西部和东北部地区。(3)生态系统服务间的权衡/协同作用存在着空间尺度效应,随着空间尺度的增加,相关性逐渐增强而显著性有所下降,且作用关系的方向性会发生改变。[结论]陕北黄土高原生态系统服务以协同为主,生态系统服务间的权衡/协同作用存在着空间尺度效应。

关键词：生态系统服务权衡/协同作用尺度效应地理分区陕北黄土高原

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